Dr. Samuel Young, head of the Research Group of Molecular Mechanisms of Synaptic Function at the Max Planck Florida Institute, together with the members of his research group, created an innovative new research technology, which has the potential to benefit researchers working to better understand the basic molecular mechanisms of how neurons operate and ultimately develop effective treatments for a host of neurological disorders such as Parkinson’s, Alzheimer’s and Huntington’s disease.
As the research group leader of the Institute’s Molecular Mechanisms of Synaptic Function group, Young and his research team spend their days studying synapses — the highly specialized contact points in the brain where neurons pass electrical and chemical signals to one another. Synapses are the fundamental units of information transfer between nerve cells, and evidence has emerged that numerous molecules control how synapses regulate how information is encoded. Synaptic malfunction, in turn, leads to severely comprised brain function, and, more importantly, it is now known that mutations in the genes that regulate synaptic function ultimately lead to the majority of neurological disorders and diseases.
In order to study synapses and understand how brain function works at the molecular level, neuroscientists use recombinant viral vectors, engineered viruses that have been stripped of their viral genome to carry transgene expression cassettes to express their gene. A transgene expression cassette is a fragment of DNA which contains the regulatory elements that are necessary for a cell to express genes of interest. However, Young found that the most commonly used transgene expression cassettes in the neuroscience field wasn’t performing at the level he needed to answer questions in his research, so out of necessity he invented pUNISHER: a high level neuro-specific transgene cassette for long-term expression in the central nervous system. pUNISHER is described in the Journal of Neurophysiology.
“Often the processes that we want to study in synaptic function are completed in tight timelines. So in order to study the role of the gene as these critical periods, one needs to express the gene, as quickly and efficiently as possible,” Young said. “Since there was a lack of existing transgene cassettes that could be used in conjunction with recombinant viral vectors, we engineered and characterized a novel transgene expression cassette, pUNISHER, which can be used in vivo or in vitro. Our findings indicated that pUNISHER led to a faster rate of onset of detectable transgene expression and at higher levels. What’s more, in conjunction with using recombinant Adenoviral vectors it allows for expression of larger cDNA’s that can’t be achieved with many current viral vectors.”
Young’s research innovation has numerous potential applications in the neuroscience field. It can be used for studying proteins at critical time periods in the creation of the function architecture of the auditory, somatosensory, or sensory systems in vivo; for the effective use of dominant negative proteins or in channelrhodopsins where high levels of expression are necessary to perturb synaptic function in vivo; or as an effective tool for expressing neuronal tracers for mapping neuronal circuits.
“I think this development has applications in the research of many neuroscientists working today, including those that need to map neuronal circuits, express proteins that are very large, or study certain drug targets,” Young said. “Our ultimate goal is that our basic research into how a molecule functions in a neuron can be used for translational research that applies to gene therapy and the treatment of neurological disorders.”
Toward that end, Young’s MPFI research group, including Dr. Monica Montesinos and graduate student Zuxin Chen, is now working in collaboration with the Discovery Biology group led by Dr. Philip LoGrasso at Scripps Florida. This research could one day provide information vital for preventing the onset of Parkinson’s.